Synergistic effect of CART (cocaine- and amphetamine-regulated transcript) peptide and cholecystokinin on food intake regulation in lean mice.
BACKGROUND
CART (cocaine- and amphetamine-regulated transcript) peptide and cholecystokinin (CCK) are neuromodulators involved in feeding behavior. This study is based on previously found synergistic effect of leptin and CCK on food intake and our hypothesis on a co-operation of the CART peptide and CCK in food intake regulation and Fos activation in their common targets, the nucleus tractus solitarii of the brainstem (NTS), the paraventricular nucleus (PVN), and the dorsomedial nucleus (DMH) of the hypothalamus.


RESULTS
In fasted C57BL/6 mice, the anorexigenic effect of CART(61-102) in the doses of 0.1 or 0.5 microg/mouse was significantly enhanced by low doses of CCK-8 of 0.4 or 4 microg/kg, while 1 mg/kg dose of CCK-A receptor antagonist devazepide blocked the effect of CART(61-102) on food intake. After simultaneous administration of 0.1 microg/mouse CART(61-102) and of 4 microg/kg of CCK-8, the number of Fos-positive neurons in NTS, PVN, and DMH was significantly higher than after administration of each particular peptide. Besides, CART(61-102) and CCK-8 showed an additive effect on inhibition of the locomotor activity of mice in an open field test.


CONCLUSIONS
The synergistic and long-lasting effect of the CART peptide and CCK on food intake and their additive effect on Fos immunoreactivity in their common targets suggest a co-operative action of CART peptide and CCK which could be related to synergistic effect of leptin on CCK satiety.
Maletínská
Lenka
L
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám, 2, 16610 Prague 6, Czech Republic. maletin@uochb.cas.cz
Maixnerová
Jana
J
Matysková
Resha
R
Haugvicová
Renata
R
Pirník
Zdeno
Z
Kiss
Alexander
A
Zelezná
Blanka
B
D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects* / Q000502:physiology; D001570:Benzodiazepinones / Q000494:pharmacology; D020109:Devazepide / Q000494:pharmacology; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000494:pharmacology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology; D013851:Thinness; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D001570:Benzodiazepinones; D006727:Hormone Antagonists; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D010671:Phenylurea Compounds; D016760:Proto-Oncogene Proteins c-fos; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; C058121:L 365260; D020109:Devazepide; D012844:Sincalide